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Title: Association of Persistent Minimal Residual Disease with Poor Outcomes of Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.
Author: Liu J, Zhao XS, Liu YR, Xu LP, Zhang XH, Chen H, Chen YH, Wang FR, Han W, Sun YQ, Yan CH, Tang FF, Mo XD, Liu KY, Fan QZ, Huang XJ, Chang YJ.
Journal: Chin Med J (Engl); 2018 Dec 05; 131(23):2808-2816. PubMed ID: 30511683.
Abstract:
BACKGROUND: Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre-HSCT. RESULTS: In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ² = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ² = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ² = 5.547, P = 0.019). In haploidentical SCT (haplo-SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre-HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo-SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo-SCT, those without persistent MRD underwent haplo-SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ² = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200-2.382, P = 0.003), worse leukemia-free survival (HR = 1.812, 95% CI: 1.168-2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528-3.627, P < 0.001). CONCLUSION: Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo-SCT settings. 异基因造血干细胞移植前流式检测微小残留病变持续阳性提示急性髓系白血病患者预后不良 摘要 背景：有研究显示流式检测的微小残留病变(Minimal residual disease,MRD)与急性髓系白血病（Acute myeloid leukemia,AML）患者预后相关。本研究旨在探讨异基因造血干细胞移植前MRD动态变化与AML患者预后的关系。 方法：回顾性分析145例于我院接受异基因造血干细胞移植的AML患者。患者移植前均为形态学完全缓解状态。用多色流式细胞术在第一和第二程化疗后、移植前检测患者骨髓MRD。 结果：接受同胞全合移植的AML患者，第一程化疗后MRD阳性组复发率较MRD阴性组高[(32.3±9.7)% vs. (7.7±3.1)%, P=0.055, χ2=3.661]，第二程化疗后MRD阳性组较MRD阴性组复发率高[(57.1±3.6)% vs. (12.5±2.7)%, P = 0.003, χ2=8.759]，移植前MRD阳性组较MRD阴性组复发率高[(50.0±9.7)% vs. (23.0±3.2)%， P = 0.019, χ2=5.547]。在单倍体移植患者，上述时间点MRD阳性组和阴性组预后无显著差异。然而，无论是接受同胞全合还是单倍体移植的患者，移植前MRD持续阳性组均较移植前MRD非持续阳性组复发率高。移植前持续MRD阳性且接受同胞全合移植组复发率最高，其次为移植前MRD持续阳性接受单倍体移植组、移植前MRD非持续阳性接受单倍体移植组，和移植前MRD非持续阳性接受同胞全合移植组[(66.7±9.2) % vs. (38.5±6.0) % vs. (18.8±8.7)% vs. (12.0±1.0)%, p < 0.001, χ2 = 20.763]。多因素分析显示，移植前MRD持续阳性预示复发风险增高(HR=1.69, 95%CI 1.200-2.382, P=0.003)，无病生存率(HR=1.812, 95%CI 1.168-2.812，P=0.008)和总体生存率降低(HR=2.354, 95%CI 1.528-3.627, P<0.001)。结论：无论接受同胞全合还是单倍体移植，移植前持续MRD阳性，而非单一时间点MRD阳性能够预示AML患者预后较差。.

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